Use the keywords feature with a free QxMD account.
Use Read by QxMD to access full text via your institution or open access sources.
Read also provides personalized recommendations to keep you up to date in your field.
Existing User
Sign InNew to Read
Sign Up#21
JOURNAL ARTICLE
Luca Vincenzo Cappelli, Danilo Fiore, Jude M Phillip, Liron Yoffe, Filomena Di Giacomo, William Chiu, Yang Hu, Clarisse Kayembe, Michael Ginsberg, Lorena Consolino, Jose Gabriel Barcia Duran, Nahuel Zamponi, Ari M Melnick, Francesco Boccalatte, Wayne Tam, Olivier Elemento, Sabina Chiaretti, Anna Guarini, Robin Foà, Leandro Cerchietti, Shahin Rafii, Giorgio Inghirami
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and often incurable disease. To uncover therapeutic vulnerabilities, we first developed T-ALL patient-derived tumor xenografts (PDXs) and exposed PDX cells to a library of 433 clinical-stage compounds in vitro. We identified 39 broadly active drugs with antileukemia activity. Because endothelial cells (ECs) can alter drug responses in T-ALL, we developed an EC/T-ALL coculture system. We found that ECs provide protumorigenic signals and mitigate drug responses in T-ALL PDXs...
February 2, 2023: Blood
#22
EDITORIAL
Ari M Melnick
In this issue of Blood Cancer Discovery, Han and colleagues find that follicular lymphomas (FL) can be stratified into distinct classes with clinical and functional relevance based on their T-cell subset composition. Their findings further indicate that pairing of FL cell MHCII expression with specific T-cell markers may represent a useful diagnostic approach to select patients for particular immunotherapies or immune augmentation therapies independent of genetic profiling. See related article by Han et al...
September 6, 2022: Blood cancer discovery
#23
REVIEW
Franck Morschhauser, Gilles Salles, Connie Lee Batlevi, Hervé Tilly, Aristeidis Chaidos, Tycel Phillips, John Burke, Ari Melnick
Enhancer of zeste homolog 2 (EZH2) is an epigenetic regulator that controls the normal biology of germinal B cells. Overexpression or mutation of EZH2 is associated with malignant transformation in a number of B-cell malignancies; thus, EZH2 inhibitors are an attractive therapeutic option for these targets. Several EZH2 inhibitors have entered clinical trials, but there remains an important question as to how EZH2 inhibitor mechanism of action differs in patients with mutant and wild-type EZH2. This review discusses the EZH2-driven mechanisms that lead to the development of B-cell lymphomas and act as therapeutic targets...
November 2022: Blood Reviews
#24
JOURNAL ARTICLE
Qianwen Hu, Tingting Xu, Min Zhang, Heng Zhang, Yongbo Liu, Hua-Bing Li, Chiqi Chen, Junke Zheng, Zhen Zhang, Fubin Li, Nan Shen, Wenqian Zhang, Ari Melnick, Chuanxin Huang
During the early phase of primary humoral responses, activated B cells can differentiate into different types of effector cells, dependent on B cell receptor affinity for antigen. However, the pivotal transcription factors governing these processes remain to be elucidated. Here, we show that transcription factor Bach2 protein in activated B cells is transiently induced by affinity-related signals and mechanistic target of rapamycin complex 1 (mTORC1)-dependent translation to restrain their expansion and differentiation into plasma cells while promoting memory and germinal center (GC) B cell fates...
July 5, 2022: Cell Reports
#25
JOURNAL ARTICLE
Min Xia, Liron David, Matt Teater, Johana Gutierrez, Xiang Wang, Cem Meydan, Andrew Lytle, Graham W Slack, David W Scott, Ryan D Morin, Ozlem Onder, Kojo S J Elenitoba-Johnson, Nahuel Zamponi, Leandro Cerchietti, Tianbao Lu, Ulrike Philippar, Lorena Fontan, Hao Wu, Ari M Melnick
UNLABELLED: Activated B cell-like diffuse large B-cell lymphomas (ABC-DLBCL) have unfavorable outcomes and chronic activation of CARD11-BCL10-MALT1 (CBM) signal amplification complexes that form due to polymerization of BCL10 subunits, which is affected by recurrent somatic mutations in ABC-DLBCLs. Herein, we show that BCL10 mutants fall into at least two functionally distinct classes: missense mutations of the BCL10 CARD domain and truncation of its C-terminal tail. Truncating mutations abrogated a motif through which MALT1 inhibits BCL10 polymerization, trapping MALT1 in its activated filament-bound state...
August 5, 2022: Cancer Discovery
#26
JOURNAL ARTICLE
Elias Campo, Elaine S Jaffe, James R Cook, Leticia Quintanilla-Martinez, Steven H Swerdlow, Kenneth C Anderson, Pierre Brousset, Lorenzo Cerroni, Laurence de Leval, Stefan Dirnhofer, Ahmet Dogan, Andrew L Feldman, Falko Fend, Jonathan W Friedberg, Philippe Gaulard, Paolo Ghia, Steven M Horwitz, Rebecca L King, Gilles Salles, Jesus San-Miguel, John F Seymour, Steven P Treon, Julie M Vose, Emanuele Zucca, Ranjana Advani, Stephen Ansell, Wing-Yan Au, Carlos Barrionuevo, Leif Bergsagel, Wing C Chan, Jeffrey I Cohen, Francesco d'Amore, Andrew Davies, Brunangelo Falini, Irene M Ghobrial, John R Goodlad, John G Gribben, Eric D Hsi, Brad S Kahl, Won-Seog Kim, Shaji Kumar, Ann S LaCasce, Camille Laurent, Georg Lenz, John P Leonard, Michael P Link, Armando Lopez-Guillermo, Maria Victoria Mateos, Elizabeth Macintyre, Ari M Melnick, Franck Morschhauser, Shigeo Nakamura, Marina Narbaitz, Astrid Pavlovsky, Stefano A Pileri, Miguel Piris, Barbara Pro, Vincent Rajkumar, Steven T Rosen, Birgitta Sander, Laurie Sehn, Margaret A Shipp, Sonali M Smith, Louis M Staudt, Catherine Thieblemont, Thomas Tousseyn, Wyndham H Wilson, Tadashi Yoshino, Pier-Luigi Zinzani, Martin Dreyling, David W Scott, Jane N Winter, Andrew D Zelenetz
Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal...
September 15, 2022: Blood
#27
JOURNAL ARTICLE
Aditya S Deshpande, Netha Ulahannan, Matthew Pendleton, Xiaoguang Dai, Lynn Ly, Julie M Behr, Stefan Schwenk, Will Liao, Michael A Augello, Carly Tyer, Priyesh Rughani, Sarah Kudman, Huasong Tian, Hannah G Otis, Emily Adney, David Wilkes, Juan Miguel Mosquera, Christopher E Barbieri, Ari Melnick, David Stoddart, Daniel J Turner, Sissel Juul, Eoghan Harrington, Marcin Imieliński
High-order three-dimensional (3D) interactions between more than two genomic loci are common in human chromatin, but their role in gene regulation is unclear. Previous high-order 3D chromatin assays either measure distant interactions across the genome or proximal interactions at selected targets. To address this gap, we developed Pore-C, which combines chromatin conformation capture with nanopore sequencing of concatemers to profile proximal high-order chromatin contacts at the genome scale. We also developed the statistical method Chromunity to identify sets of genomic loci with frequencies of high-order contacts significantly higher than background ('synergies')...
October 2022: Nature Biotechnology
#28
REVIEW
Antonin Papin, Ethel Cesarman, Ari Melnick
In eukaryotic cells, the genome is three dimensionally (3D) organized with DNA interaction dynamics and topology changes that regulate gene expression and drive cell fate. Upon antigen stimulation, naive B cells are activated and form germinal centers (GC) for the generation of memory B cells and plasma cells. Thereby, terminal B-cell differentiation and associated humoral immune response require massive but rigorous 3D DNA reorganization. Here, we review the dynamics of genome reorganization during GC formation and the impact of its alterations on lymphomagenesis from the nucleosome structure to the higher order chromosome organization...
June 2022: Current Opinion in Genetics & Development
#29
JOURNAL ARTICLE
Ekaterina Kots, Coraline Mlynarczyk, Ari Melnick, George Khelashvili
B-cell translocation gene 1 (BTG1) protein belongs to the BTG/TOB (transducer of ERBB2) family of antiproliferative proteins whose members regulate various key cellular processes such as cell cycle progression, apoptosis, and differentiation. Somatic missense mutations in BTG1 are found in ∼70% of a particularly malignant and disseminated subtype of diffuse large B-cell lymphoma (DLBCL). Antiproliferative activity of BTG1 has been linked to its ability to associate with transcriptional cofactors and various enzymes...
April 21, 2022: Biophysical Journal
#30
JOURNAL ARTICLE
Wilfred Leung, Matt Teater, Ceyda Durmaz, Cem Meydan, Alexandra G Chivu, Amy Chadburn, Edward J Rice, Ashlesha Muley, Jeannie M Camarillo, Jaison Arivalagan, Ziyi Li, Christopher R Flowers, Neil L Kelleher, Charles G Danko, Marcin Imielinski, Sandeep S Dave, Scott A Armstrong, Christopher E Mason, Ari M Melnick
UNLABELLED: SETD2 is the sole histone methyltransferase responsible for H3K36me3, with roles in splicing, transcription initiation, and DNA damage response. Homozygous disruption of SETD2 yields a tumor suppressor effect in various cancers. However, SETD2 mutation is typically heterozygous in diffuse large B-cell lymphomas. Here we show that heterozygous Setd2 deficiency results in germinal center (GC) hyperplasia and increased competitive fitness, with reduced DNA damage checkpoint activity and apoptosis, resulting in accelerated lymphomagenesis...
July 6, 2022: Cancer Discovery
#31
JOURNAL ARTICLE
Katsuyoshi Takata, Lauren C Chong, Daisuke Ennishi, Tomohiro Aoki, Michael Yu Li, Avinash Thakur, Shannon Healy, Elena Viganò, Tao Dao, Daniel Kwon, Gerben Duns, Julie S Nielsen, Susana Ben-Neriah, Ethan Tse, Stacy S Hung, Merrill Boyle, Sung Soo Mun, Christopher M Bourne, Bruce Woolcock, Adèle H Telenius, Makoto Kishida, Shinya Rai, Allen W Zhang, Ali Bashashati, Saeed Saberi, Gianluca D' Antonio, Brad H Nelson, Sohrab P Shah, Pamela A Hoodless, Ari M Melnick, Randy D Gascoyne, Joseph M Connors, David A Scheinberg, Wendy Béguelin, David W Scott, Christian Steidl
PRAME is a prominent member of the cancer germline antigen family of proteins, which triggers autologous T-cell mediated immune responses. Integrative genomic analysis in diffuse large B-cell lymphoma (DLBCL) uncovered recurrent, and highly focal deletions of 22q11.22 including the PRAME gene, which were associated with poor outcome. PRAME-deleted tumors showed cytotoxic T-cell immune escape and were associated with cold tumor microenvironments. In addition, PRAME down-modulation was strongly associated with somatic EZH2 Y641 mutations in DLBCL...
April 5, 2022: Journal of Clinical Investigation
#32
JOURNAL ARTICLE
Kibaek Choe, Yusaku Hontani, Tianyu Wang, Eric Hebert, Dimitre G Ouzounov, Kristine Lai, Ankur Singh, Wendy Béguelin, Ari M Melnick, Chris Xu
Intravital confocal microscopy and two-photon microscopy are powerful tools to explore the dynamic behavior of immune cells in mouse lymph nodes (LNs), with penetration depth of ~100 and ~300 μm, respectively. Here, we used intravital three-photon microscopy to visualize the popliteal LN through its entire depth (600-900 μm). We determined the laser average power and pulse energy that caused measurable perturbation in lymphocyte migration. Long-wavelength three-photon imaging within permissible parameters was able to image the entire LN vasculature in vivo and measure CD8+ T cells and CD4+ T cell motility in the T cell zone over the entire depth of the LN...
January 27, 2022: Nature Immunology
#33
JOURNAL ARTICLE
Meng Li, Matthew R Teater, Jun Young Hong, Noel R Park, Cihangir Duy, Hao Shen, Ling Wang, Zhengming Chen, Leandro Cerchietti, Shawn M Davidson, Hening Lin, Ari M Melnick
Diffuse large B-cell lymphomas (DLBCL) are broadly dependent on anaplerotic metabolism regulated by mitochondrial SIRT3. Herein we find that translational upregulation of ATF4 is coupled with anaplerotic metabolism in DLBCLs due to nutrient deprivation caused by SIRT3 driving rapid flux of glutamine into the tricarboxylic acid (TCA) cycle. SIRT3 depletion led to ATF4 downregulation and cell death, which was rescued by ectopic ATF4 expression. Mechanistically, ATF4 translation is inhibited in SIRT3-deficient cells due to the increased pools of amino acids derived from compensatory autophagy and decreased glutamine consumption by the TCA cycle...
January 2022: Blood cancer discovery
#34
COMMENT
Meng Li, Ari M Melnick
In this issue of Blood Cancer Discovery , Yan and colleagues discovered that mitochondrial deacylase, SIRT5, is required in AML cells to support mitochondrial oxidative phosphorylation, maintain redox homeostasis, and drive glutaminolysis. The new SIRT5 inhibitor, NRD167, can efficiently target SIRT5 in AMLs at micromolar range and may constitute a novel therapeutic approach to improve clinical outcomes of patients with AML. See related article by Yan et al., p. 266.
May 2021: Blood cancer discovery
#35
JOURNAL ARTICLE
Maciej Giefing, Micah D Gearhart, Markus Schneider, Birte Overbeck, Wolfram Klapper, Sylvia Hartmann, Adam Ustaszewski, Marc A Weniger, Laura Wiehle, Martin-Leo Hansmann, Ari Melnick, Wendy Béguelin, Christer Sundström, Ralf Küppers, Vivian J Bardwell, Reiner Siebert
BCOR is a component of a variant Polycomb repressive complex 1 (PRC1.1). PRC1 and PRC2 complexes together constitute a major gene regulatory system critical for appropriate cellular differentiation. The gene is upregulated in germinal center (GC) B cells and mutated in a number of hematologic malignancies. We report BCOR inactivating alterations in 4/7 classic Hodgkin lymphoma (cHL) cell lines, subclonal somatic mutations in Hodgkin and Reed-Sternberg (HRS) cells of 4/10 cHL cases, and deletions in HRS cells of 7/17 primary cHL cases...
December 27, 2021: Leukemia & Lymphoma
#36
Jonathan Foox, Jessica Nordlund, Claudia Lalancette, Ting Gong, Michelle Lacey, Samantha Lent, Bradley W Langhorst, V K Chaithanya Ponnaluri, Louise Williams, Karthik Ramaswamy Padmanabhan, Raymond Cavalcante, Anders Lundmark, Daniel Butler, Christopher Mozsary, Justin Gurvitch, John M Greally, Masako Suzuki, Mark Menor, Masaki Nasu, Alicia Alonso, Caroline Sheridan, Andreas Scherer, Stephen Bruinsma, Gosia Golda, Agata Muszynska, Paweł P Łabaj, Matthew A Campbell, Frank Wos, Amanda Raine, Ulrika Liljedahl, Tomas Axelsson, Charles Wang, Zhong Chen, Zhaowei Yang, Jing Li, Xiaopeng Yang, Hongwei Wang, Ari Melnick, Shang Guo, Alexander Blume, Vedran Franke, Inmaculada Ibanez de Caceres, Carlos Rodriguez-Antolin, Rocio Rosas, Justin Wade Davis, Jennifer Ishii, Dalila B Megherbi, Wenming Xiao, Will Liao, Joshua Xu, Huixiao Hong, Baitang Ning, Weida Tong, Altuna Akalin, Yunliang Wang, Youping Deng, Christopher E Mason
No abstract text is available yet for this article.
December 23, 2021: Genome Biology
#37
JOURNAL ARTICLE
Jonathan Foox, Jessica Nordlund, Claudia Lalancette, Ting Gong, Michelle Lacey, Samantha Lent, Bradley W Langhorst, V K Chaithanya Ponnaluri, Louise Williams, Karthik Ramaswamy Padmanabhan, Raymond Cavalcante, Anders Lundmark, Daniel Butler, Christopher Mozsary, Justin Gurvitch, John M Greally, Masako Suzuki, Mark Menor, Masaki Nasu, Alicia Alonso, Caroline Sheridan, Andreas Scherer, Stephen Bruinsma, Gosia Golda, Agata Muszynska, Paweł P Łabaj, Matthew A Campbell, Frank Wos, Amanda Raine, Ulrika Liljedahl, Tomas Axelsson, Charles Wang, Zhong Chen, Zhaowei Yang, Jing Li, Xiaopeng Yang, Hongwei Wang, Ari Melnick, Shang Guo, Alexander Blume, Vedran Franke, Inmaculada Ibanez de Caceres, Carlos Rodriguez-Antolin, Rocio Rosas, Justin Wade Davis, Jennifer Ishii, Dalila B Megherbi, Wenming Xiao, Will Liao, Joshua Xu, Huixiao Hong, Baitang Ning, Weida Tong, Altuna Akalin, Yunliang Wang, Youping Deng, Christopher E Mason
BACKGROUND: Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and cross-validated resource for epigenetics research from the FDA's Epigenomics Quality Control Group...
December 6, 2021: Genome Biology
#38
REVIEW
Madhav R Seshadri, Ari M Melnick
The activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) has an aggressive course and is associated with poor prognosis in the relapsed or refractory setting. ABC-DLBCL is characterized by chronic active signaling of NF-κB, which is dependent on the CARD11-BCL10-MALT1 (CBM) complex. MALT1 is a key effector of the CBM complex and activates canonical NF-κB and AP-1 among other transcription factors via distinct protease and scaffold functions. There is therefore growing interest in therapeutic targeting of MALT1 for B-cell malignancies...
April 2022: Leukemia & Lymphoma
#39
COMMENT
Meng Li, Ari M Melnick
In this issue of Blood Cancer Discovery , Yan and colleagues discovered that mitochondrial deacylase, SIRT5, is required in AML cells to support mitochondrial oxidative phosphorylation, maintain redox homeostasis, and drive glutaminolysis. The new SIRT5 inhibitor, NRD167, can efficiently target SIRT5 in AMLs at micromolar range and may constitute a novel therapeutic approach to improve clinical outcomes of patients with AML. See related article by Yan et al., p. 266.
May 2021: Blood cancer discovery
#40
JOURNAL ARTICLE
Martin A Rivas, Ceyda Durmaz, Andreas Kloetgen, Cristopher R Chin, Zhengming Chen, Bhavneet Bhinder, Amnon Koren, Aaron D Viny, Christopher D Scharer, Jeremy M Boss, Olivier Elemento, Christopher E Mason, Ari M Melnick
The cohesin complex plays critical roles in genomic stability and gene expression through effects on 3D architecture. Cohesin core subunit genes are mutated across a wide cross-section of cancers, but not in germinal center (GC) derived lymphomas. In spite of this, haploinsufficiency of cohesin ATPase subunit Smc3 was shown to contribute to malignant transformation of GC B-cells in mice. Herein we explored potential mechanisms and clinical relevance of Smc3 deficiency in GC lymphomagenesis. Transcriptional profiling of Smc3 haploinsufficient murine lymphomas revealed downregulation of genes repressed by loss of epigenetic tumor suppressors Tet2 and Kmt2d ...
2021: Frontiers in Immunology
Make the most of Read.
Download the mobile app.
Download the mobile app.
Fetching more papers... 
